Nuclear localization and intensity of staining of nm23 protein is useful marker for breast cancer progression

Ismail, Nawfal; Kaur, Gurjeet; Hashim, Hasnah; Hassan, Mohammed

doi:10.1186/1475-2867-8-6

Cited by 14 publications

(8 citation statements)

References 22 publications

(17 reference statements)

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“…We observed that LY2109761 reduced MMP-9 in liver metastases in treated mice, whereas the MMP-2 level remained unchanged (Figure 4A). The level of nm23 is increased in highly metastatic malignancies 16, 17, 18. We observed that LY2109761 significantly reduces nm23 expression in liver metastases of treated mice when compared with control mice (Figure 4A).…”

Section: Resultsmentioning

confidence: 78%

“…Apart from this, LY2109761 also down-regulated pro-oncogenic/pro-metastatic proteins like MMP-9, uPA, and COX-2; all of which are known to be induced by TGF-β and in turn promote colorectal cancer progression. Although, reduced level of nm23 expression has been shown to be associated with aggressive tumor behavior21, high levels of nm23 expression were also noted in the advanced stages of colon, breast and thyroid carcinomas 16, 17, 18. In addition, in a related study nm23 has been shown to be upregulated in liver metastatsis in a splenic injection model 15.…”

Section: Discussionmentioning

confidence: 96%

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Antimetastatic Role of Smad4 Signaling in Colorectal Cancer

et al. 2010

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Background & Aims-Transforming growth factor (TGF)-β signaling occurs through Smads 2/3/4, which translocate to the nucleus to regulate transcription; TGF-β has tumor suppressive effects in some tumor models and pro-metastatic effects in others. In patients with colorectal cancer (CRC), mutations or reduced levels of Smad4 have been correlated with reduced survival. However, the function of Smad signaling and the effects of TGF-β receptor kinase inhibitors (TRKI) have not been analyzed during CRC metastasis. We investigated the role of TGF-β/Smad signaling in CRC progression.

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Section: Resultsmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 96%

Antimetastatic Role of Smad4 Signaling in Colorectal Cancer

et al. 2010

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“…9 Nuclear NME1 was observed at a higher frequency in invasive ductal carcinoma and invasive lobular carcinoma node-positive patients compared with node-negative patients, suggesting that nuclear NME1 may be a useful prognostic marker for poor outcome in breast cancer. 8 The contribution of nuclear NME1 to the poor prognosis of breast and prostate cancer 8,9 patients is currently unclear. In contrast, nuclear NME1 correlates with a favorable prognosis in laryngeal carcinoma patients.…”

Section: Nuclear Nme1 As a Potential Prognostic Marker In Cancermentioning

confidence: 99%

Nuclear functions of NME proteins

Puts

Leonard

Pamidimukkala

et al. 2018

Laboratory Investigation

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The NME family of proteins is composed of 10 isoforms, designated NME1-10, which are diverse in their enzymatic activities and patterns of subcellular localization. Each contains a conserved domain associated with a nucleoside diphosphate kinase (NDPK) function, although not all are catalytically active. Several of the NME isoforms (NME1, NME5, NME7, and NME8) also exhibit a 3′–5′ exonuclease activity, suggesting roles in DNA proofreading and repair. NME1 and NME2 have been shown to translocate to the nucleus, although they lack a canonical nuclear localization signal. Binding of NME1 and NME2 to DNA does not appear to be sequence-specific in a strict sense, but instead is directed to single-stranded regions and/or other non-B-form structures. NME1 and NME2 have been identified as potential canonical transcription factors that regulate gene transcription through their DNA-binding activities. Indeed, the NME1 and NME2 isoforms have been shown to regulate gene expression programs in a number of cellular settings, and this regulatory function has been proposed to underlie their well-recognized ability to suppress the metastatic phenotype of cancer cells. Moreover, NME1 and, more recently, NME3, have been implicated in repair of both single- and double-stranded breaks in DNA. This suggests that reduced expression of NME proteins could contribute to the genomic instability that drives cancer progression. Clearly, a better understanding of the nuclear functions of NME1 and possibly other NME isoforms could provide critical insights into mechanisms underlying malignant progression in cancer. Indeed, clinical data indicate that the subcellular localization of NME1 may be an important prognostic marker in some cancers. This review summarizes putative functions of nuclear NME proteins in DNA binding, transcription, and DNA damage repair, and highlights their possible roles in cancer progression.

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“…However, Epstein-Barr virus nuclear antigen 3C (EBNA-3C) promotes Nm23-H1 nuclear localization and modulate Nm23-H1 activities [46]. Ismail et al [47] showed that nuclear localization of NM23-H1 protein in breast cancer is seen more frequently in node-positive metastatic cases. They concluded that abnormal nuclear accumulation of the protein may indicate tumor progression [47].…”

Section: Discussionmentioning

confidence: 99%

“…Ismail et al [47] showed that nuclear localization of NM23-H1 protein in breast cancer is seen more frequently in node-positive metastatic cases. They concluded that abnormal nuclear accumulation of the protein may indicate tumor progression [47]. Similarly, we demonstrated that nuclear NM23-H1 was significantly positively correlated with stage.…”

Section: Discussionmentioning

confidence: 99%

Metastasis suppressor proteins in cutaneous squamous cell carcinoma

Bozdoğan

Vargel

Çavuşoğlu

et al. 2016

Pathology - Research and Practice

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Cutaneous squamous cell carcinomas (cSCCs) are common human carcinomas. Despite having metastasizing capacities, they usually show less aggressive progression compared to squamous cell carcinoma (SCC) of other organs. Metastasis suppressor proteins (MSPs) are a group of proteins that control and slow-down the metastatic process. In this study, we established the importance of seven well-defined MSPs including NDRG1, NM23-H1, RhoGDI2, E-cadherin, CD82/KAI1, MKK4, and AKAP12 in cSCCs. Protein expression levels of the selected MSPs were detected in 32 cSCCs, 6 in situ SCCs, and two skin cell lines (HaCaT, A-431) by immunohistochemistry. The results were evaluated semi-quantitatively using the HSCORE system. In addition, mRNA expression levels were detected by qRT-PCR in the cell lines. The HSCOREs of NM23-H1 were similar in cSCCs and normal skin tissues, while RGHOGDI2, E-cadherin and AKAP12 were significantly downregulated in cSCCs compared to normal skin. The levels of MKK4, NDRG1 and CD82 were partially conserved in cSCCs. In stage I SCCs, nuclear staining of NM23-H1 (NM23-H1nuc) was significantly lower than in stage II/III SCCs. Only nuclear staining of MKK4 (MKK4nuc) showed significantly higher scores in in situ carcinomas compared to invasive SCCs. In conclusion, similar to other human tumors, we have demonstrated complex differential expression patterns for the MSPs in in-situ and invasive cSCCs. This complex MSP signature warrants further biological and experimental pathway research.

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Nuclear localization and intensity of staining of nm23 protein is useful marker for breast cancer progression

Cited by 14 publications

References 22 publications

Antimetastatic Role of Smad4 Signaling in Colorectal Cancer

Antimetastatic Role of Smad4 Signaling in Colorectal Cancer

Nuclear functions of NME proteins

Metastasis suppressor proteins in cutaneous squamous cell carcinoma

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